Evaluating the tumor biology of lung adenocarcinoma: A multimodal analysis.
ABSTRACT: We evaluated the relationships among functional imaging modality such as PET-CT and DW-MRI and lung adenocarcinoma pathologic heterogeneity, extent of invasion depth, and tumor cellularity as a marker of tumor microenvironment.In total, 74 lung adenocarcinomas were prospectively included. All patients underwent 18F-fluorodeoxyglucose (FDG) PET-CT and MRI before curative surgery. Pathology revealed 68 stage I tumors, 3 stage II tumors, and 3 stage IIIA tumors. Comprehensive histologic subtyping was performed for all surgically resected tumors. Maximum standardized uptake value (SUVmax) and ADC values were correlated with pathologic grade, extent of invasion, solid tumor size, and tumor cellularity.Mean solid tumor size (low: 1.7?±?3.0?mm, indeterminate: 13.9?±?14.2?mm, and high grade: 30.3?±?13.5?mm) and SUVmax (low: 1.5?±?0.2, indeterminate: 3.5?±?2.5, and high grade: 15.3?±?0) had a significant relationship with pathologic grade based on 95% confidence intervals (P?=?.01 and P?
Project description:Metabolism and water diffusion may have a relationship or an effect on each other in the same tumor. Knowledge of their relationship could expand the understanding of tumor biology and serve the field of oncologic imaging. This study aimed to evaluate the relationship between metabolism and water diffusivity in hepatic tumors using a simultaneous positron emission tomography/magnetic resonance imaging (PET/MRI) system with F-18 fluorodeoxyglucose (FDG) and to reveal the metabolic and diffusional characteristics of each type of hepatic tumor.Forty-one patients (mean age 63 ± 13 years, 31 male) with hepatic tumors (18 hepatocellular carcinoma [HCC], six cholangiocarcinoma [CCC], 10 metastatic tumors, one neuroendocrine malignancy, and six benign lesions) underwent FDG PET/MRI before treatment. Maximum standard uptake (SUVmax) values from FDG PET and the apparent diffusion coefficient (ADC) from the diffusion-weighted images were obtained for the tumor and their relationships were examined. We also investigated the difference in SUVmax and ADC for each type of tumor.SUVmax showed a negative correlation with ADC (r = -0.404, p = 0.009). The median of SUVmax was 3.22 in HCC, 6.99 in CCC, 6.30 in metastatic tumors, and 1.82 in benign lesions. The median of ADC was 1.039 × 10-3 mm/s2 in HCC, 1.148 × 10-3 mm/s2 in CCC, 0.876 × 10-3 mm/s2 in metastatic tumors, and 1.323 × 10-3 mm/s2 in benign lesions. SUVmax was higher in metastatic tumors than in benign lesions (p = 0.023). Metastatic tumors had a lower ADC than CCC (p = 0.039) and benign lesions (p = 0.004). HCC had a lower ADC than benign lesions, with a suggestive trend (p = 0.06).Our results indicate that SUVmax is negatively correlated with ADC in hepatic tumors, and each group of tumors has different metabolic and water diffusivity characteristics. Evaluation of hepatic tumors by PET/MRI could be helpful in understanding tumor characteristics.
Project description:PURPOSE:Investigating the diagnostic accuracy of histogram analyses of apparent diffusion coefficient (ADC) values for determining non-small cell lung cancer (NSCLC) tumor grades, lymphovascular invasion, and pleural invasion. MATERIALS AND METHODS:We studied 60 surgically diagnosed NSCLC patients. Diffusion-weighted imaging (DWI) was performed in the axial plane using a navigator-triggered single-shot, echo-planar imaging sequence with prospective acquisition correction. The ADC maps were generated, and we placed a volume-of-interest on the tumor to construct the whole-lesion histogram. Using the histogram, we calculated the mean, 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles of ADC, skewness, and kurtosis. Histogram parameters were correlated with tumor grade, lymphovascular invasion, and pleural invasion. We performed a receiver operating characteristics (ROC) analysis to assess the diagnostic performance of histogram parameters for distinguishing different pathologic features. RESULTS:The ADC mean, 10th, 25th, 50th, 75th, 90th, and 95th percentiles showed significant differences among the tumor grades. The ADC mean, 25th, 50th, 75th, 90th, and 95th percentiles were significant histogram parameters between high- and low-grade tumors. The ROC analysis between high- and low-grade tumors showed that the 95th percentile ADC achieved the highest area under curve (AUC) at 0.74. Lymphovascular invasion was associated with the ADC mean, 50th, 75th, 90th, and 95th percentiles, skewness, and kurtosis. Kurtosis achieved the highest AUC at 0.809. Pleural invasion was only associated with skewness, with the AUC of 0.648. CONCLUSIONS:ADC histogram analyses on the basis of the entire tumor volume are able to stratify NSCLCs' tumor grade, lymphovascular invasion and pleural invasion.
Project description:This study investigated the spatial relationship of 2-deoxy-2-[18F]-fluoro-D-glucose positron emission tomography ([18F]FDG-PET) standardized uptake values (SUVs) and apparent diffusion coefficients (ADCs) derived from magnetic resonance (MR) diffusion imaging on a voxel level using simultaneously acquired PET/MR data. We performed an institutional retrospective analysis of patients with newly diagnosed cervical cancer who received a pre-treatment simultaneously acquired [18F]FDG-PET/MR. Voxel SUV and ADC values, and global tumor metrics including maximum SUV (SUVmax), mean ADC (ADCmean), and mean tumor-to-muscle ADC ratio (ADCT/M) were compared. The impacts of histology, grade, and tumor volume on the voxel SUV to ADC relationship were also evaluated. The potential prognostic value of the voxel SUV/ADC relationship was evaluated in an exploratory analysis using Kaplan-Meier/log-rank and univariate Cox analysis.Seventeen patients with PET/MR scans were identified. There was a significant inverse correlation between SUVmax and ADCmean, and SUVmax and ADCT/M. In the voxelwise analysis, squamous cell carcinomas (SCCAs) and poorly differentiated tumors showed a consistent significant inverse correlation between voxel SUV and ADC values; adenocarcinomas (AdenoCAs) and well/moderately differentiated tumors did not. The strength of the voxel SUV/ADC correlation varied with metabolic tumor volume (MTV). On log-rank analysis, the correlation between voxel SUV/ADC values was prognostic of disease-free survival (DFS).In this hypothesis-generating study, a consistent inverse correlation between voxel SUV and ADC values was seen in SCCAs and poorly differentiated tumors. On univariate statistical analysis, correlation between voxel SUV and ADC values was prognostic for DFS.
Project description:Differentiating benign from malignant peripheral nerve sheath tumors can be very challenging using conventional MR imaging. Our aim was to test the hypothesis that conventional and functional MR imaging can accurately diagnose malignancy in patients with indeterminate peripheral nerve sheath tumors.This institutional review board-approved, Health Insurance Portability and Accountability Act-compliant study retrospectively reviewed 61 consecutive patients with 80 indeterminate peripheral nerve sheath tumors. Of these, 31 histologically proved peripheral nerve sheath tumors imaged with conventional (unenhanced T1, fluid-sensitive, contrast-enhanced T1-weighted sequences) and functional MR imaging (DWI/apparent diffusion coefficient mapping, dynamic contrast-enhanced MR imaging) were included. Two observers independently assessed anatomic (size, morphology, signal) and functional (ADC values, early arterial enhancement by dynamic contrast-enhanced MR) features to determine interobserver agreement. The accuracy of MR imaging for differentiating malignant from benign was also determined by receiver operating characteristic analysis.Of 31 peripheral nerve sheath tumors, there were 9 malignant (9%) and 22 benign ones (81%). With anatomic sequences, average tumor diameter (6.3 ± 1.8 versus 3.9 ± 2.3 mm, P = .009), ill-defined/infiltrative margins (77% versus 32%; P = .04), and the presence of peritumoral edema (66% versus 23%, P = .01) were different for malignant peripheral nerve sheath tumors and benign peripheral nerve sheath tumors. With functional sequences, minimum ADC (0.47 ± 0.32 × 10(-3) mm(2)/s versus 1.08 ± 0.26 × 10(-3) mm(2)/s; P < .0001) and the presence of early arterial enhancement (50% versus 11%; P = .03) were different for malignant peripheral nerve sheath tumors and benign peripheral nerve sheath tumors. The minimum ADC (area under receiver operating characteristic curve was 0.89; 95% confidence interval, 0.73-0.97) and the average tumor diameter (area under the curve = 0.8; 95% CI, 0.66-0.94) were accurate in differentiating malignant peripheral nerve sheath tumors from benign peripheral nerve sheath tumors. With threshold values for minimum ADC ? 1.0 × 10(-3) mm(2)/s and an average diameter of ?4.2 cm, malignancy could be diagnosed with 100% sensitivity (95% CI, 66.4%-100%).Average tumor diameter and minimum ADC values are potentially important parameters that may be used to distinguish malignant peripheral nerve sheath tumors from benign peripheral nerve sheath tumors.
Project description:PURPOSE: We evaluate a novel magnetic resonance imaging (MRI) technique to improve detection of aggressive prostate cancer (PCa). MATERIALS AND METHODS: We performed a retrospective analysis of pre-surgical prostate MRI scans using an advanced diffusion-weighted imaging technique called restriction spectrum imaging (RSI), which can be presented as a normalized z-score statistic. Scans were acquired prior to radical prostatectomy. Prostatectomy specimens were processed using whole-mount sectioning and regions of interest (ROIs) were drawn around individual PCa tumors. Corresponding ROIs were drawn on the MRI imaging and paired with ROIs in regions with no pathology. RSI z-score and conventional apparent diffusion coefficient (ADC) values were recorded for each ROI. Paired t-test, ANOVA, and logistic regression analyses were performed. RESULTS: We evaluated 28 patients with 64 ROIs (28 benign and 36 PCa). The mean difference in RSI z-score (PCa ROI-Benign ROI) was 2.17 (SE?=?0.11; p?<?0.001) and in ADC was 551?mm(2)/s (SE?=?80?mm(2)/s; paired t-test, p?<?0.001). The differences in the means among all groups (benign, primary Gleason 3, and primary Gleason 4) was significant for both RSI z-score (F 3,64?=?97.7, p?<?0.001) and ADC (F 3,64?=?13.9, p?<?0.001). A t-test was performed on only PCa tumor ROIs (n?=?36) to determine PCa aggressiveness (Gleason 3 vs. Gleason 4) revealing that RSI z-score was still significant (p?=?0.03), whereas, ADC values were no longer significant (p?=?0.08). In multivariable analysis adjusting for age and race, RSI z-score was associated with PCa aggressiveness (OR 10.3, 95% CI: 1.4-78.0, p?=?0.02) while ADC trended to significance (p?=?0.07). CONCLUSION: The RSI-derived normalized cellularity index is associated with aggressive PCa as determined by pathologic Gleason scores. Further utilization of RSI techniques may serve to enhance standardized reporting systems for PCa in the future.
Project description:To retrospectively determine the accuracy of diffusion-weighted (DW) magnetic resonance (MR) imaging for identifying cancer in the prostate peripheral zone (PZ) and to assess the accuracy of tumor volume measurements made with T2-weighted imaging and combined T2-weighted and DW MR imaging by using surgical pathologic examination as the reference standard.The institutional review board issued a waiver of informed consent for this HIPAA-compliant study. Forty-two patients underwent endorectal MR at 1.5 T before undergoing radical prostatectomy for prostate cancer and had at least one PZ tumor larger than 0.1 cm(3) at surgical pathologic examination. On T2-weighted images, an experienced radiologist outlined suspected PZ tumors. Two apparent diffusion coefficient (ADC) cutoff values were identified by using the Youden index and published literature. Image cluster analysis was performed on voxels within the suspected tumor regions. Associations between volume measurements from imaging and from pathologic examination were assessed by using concordance correlation coefficients (CCCs). The sensitivity and specificity of ADCs for identifying malignant PZ voxels were calculated.In identifying malignant voxels, respective ADC cutoff values of 0.0014 and 0.0016 mm(2)/sec yielded sensitivity of 82% and 95% and specificity of 85% and 65%, respectively. Sixty PZ cancer lesions larger than 0.1 cm(3) were found at pathologic examination; 43 were detected by the radiologist. CCCs between imaging and pathologic tumor volume measurements were 0.36 for T2-weighted imaging, and 0.46 and 0.60 for combined T2-weighted and DW MR imaging with ADC cutoffs of 0.0014 and 0.0016 mm(2)/sec, respectively; the CCC of combined T2-weighted and DW MR imaging (ADC cutoff, 0.0016 mm(2)/sec) was significantly higher (P = .006) than that of T2-weighted imaging alone.Adding DW MR to T2-weighted imaging can significantly improve the accuracy of prostate PZ tumor volume measurement.http://radiology.rsnajnls.org/cgi/content/full/252/2/449/DC1.
Project description:Several studies have analyzed a correlation between the apparent diffusion coefficient (ADC) derived from diffusion-weighted MRI and the tumor cellularity of corresponding histopathological specimens in brain tumors with inconclusive findings. Here, we compared a large dataset of ADC and cellularity values of stereotactic biopsies of glioblastoma patients using a new postprocessing approach including trajectory analysis and automatic nuclei counting.Thirty-seven patients with newly diagnosed glioblastomas were enrolled in this study. ADC maps were acquired preoperatively at 3T and coregistered to the intraoperative MRI that contained the coordinates of the biopsy trajectory. 561 biopsy specimens were obtained; corresponding cellularity was calculated by semi-automatic nuclei counting and correlated to the respective preoperative ADC values along the stereotactic biopsy trajectory which included areas of T1-contrast-enhancement and necrosis.There was a weak to moderate inverse correlation between ADC and cellularity in glioblastomas that varied depending on the approach towards statistical analysis: for mean values per patient, Spearman's ? = -0.48 (p = 0.002), for all trajectory values in one joint analysis Spearman's ? = -0.32 (p < 0.001). The inverse correlation was additionally verified by a linear mixed model.Our data confirms a previously reported inverse correlation between ADC and tumor cellularity. However, the correlation in the current article is weaker than the pooled correlation of comparable previous studies. Hence, besides cell density, other factors, such as necrosis and edema might influence ADC values in glioblastomas.
Project description:Recent conflicting reports have found both brain tumor hypercellularity and necrosis in regions of restricted diffusion on MRI-derived apparent diffusion coefficient (ADC) images. This study precisely compares ADC and cell density voxel by voxel using postmortem human whole brain samples.Patients with meningioma were evaluated to determine a normative ADC distribution within benign fluid attenuated inversion recovery (FLAIR) T2/hyperintensity surrounding tumor. This distribution was used to calculate a minimum ADC threshold to define regions of ADC-FLAIR mismatch (AFMM), where restricted diffusion presented in conjunction with T2/FLAIR hyperintensity. Contrast-enhancing voxels were excluded from this analysis. AFMM maps were generated using imaging acquired prior to death in 7 patients with high-grade glioma who eventually donated their brains upon death. Histological samples were taken from numerous regions of abnormal FLAIR and AFMM. Each sample was computationally processed to determine cell density. Custom software was then used to downsample coregistered microscopic histology to the more coarse MRI resolution. A voxel-by-voxel evaluation comparing ADC and cellularity was then performed.An ADC threshold of 0.929 × 10(-3) mm(2)/s was calculated from meningioma-induced edema and was used to define AFMM. Regions of AFMM showed significantly greater cell density in 6 of 7 high-grade glioma cases compared with regions of hyperintense FLAIR alone (P < .0001). Two patients had small regions of diffusion-restricted necrosis that had significantly lower ADC than nearby hypercellularity.Regions of AFMM contain hypercellularity except for regions with extremely restricted diffusion, where necrosis is present.
Project description:OBJECTIVE: To perform a meta-analysis exploring the correlation between the apparent diffusion coefficient (ADC) and tumor cellularity in patients. MATERIALS AND METHODS: We searched medical and scientific literature databases for studies discussing the correlation between the ADC and tumor cellularity in patients. Only studies that were published in English or Chinese prior to November 2012 were considered for inclusion. Summary correlation coefficient (r) values were extracted from each study, and 95% confidence intervals (CIs) were calculated. Sensitivity and subgroup analyses were performed to investigate potential heterogeneity. RESULTS: Of 189 studies, 28 were included in the meta-analysis, comprising 729 patients. The pooled r for all studies was -0.57 (95% CI: -0.62, -0.52), indicating notable heterogeneity (P<0.001). After the sensitivity analysis, two studies were excluded, and the pooled r was -0.61 (95% CI: -0.66, -0.56) and was not significantly heterogeneous (P?=?0.127). Regarding tumor type subgroup analysis, there were sufficient data to support a strong negative correlation between the ADC and cellularity for brain tumors. There was no notable evidence of publication bias. CONCLUSIONS: There is a strong negative correlation between the ADC and tumor cellularity in patients, particularly in the brain. However, larger, prospective studies are warranted to validate these findings in other cancer types.
Project description:Previous non-simultaneous PET/MR studies have shown heterogeneous results about the correlation between standardized uptake values (SUVs) and apparent diffusion coefficients (ADCs). The aim of this study was to investigate correlations in patients with primary and recurrent tumors using a simultaneous PET/MRI system which could lead to a better understanding of tumor biology and might play a role in early response assessment.We included 31 patients with histologically confirmed primary (n = 14) or recurrent cervical cancer (n = 17) who underwent simultaneous whole-body 18F-FDG-PET/MRI comprising DWI. Image analysis was performed by a radiologist and a nuclear physician who identified tumor margins and quantified ADC and SUV. Pearson correlations were calculated to investigate the association between ADC and SUV.92 lesions were detected. We found a significant inverse correlation between SUVmax and ADCmin (r = -0.532, p = 0.05) in primary tumors as well as in primary metastases (r = -0.362, p = 0.05) and between SUVmean and ADCmin (r = -0.403, p = 0.03). In recurrent local tumors we found correlations for SUVmax and ADCmin (r = -0.747, p = 0.002) and SUVmean and ADCmin (r = -0.773, p = 0.001). Associations for recurrent metastases were not significant (p>0.05).Our study demonstrates the feasibility of fast and reliable measurement of SUV and ADC with simultaneous PET/MRI. In patients with cervical cancer we found significant inverse correlations for SUV and ADC which could play a major role for further tumor characterization and therapy decisions.